The pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models

J M A van den Brand, B L Haagmans, D van Riel, A D M E Osterhaus, T Kuiken, J M A van den Brand, B L Haagmans, D van Riel, A D M E Osterhaus, T Kuiken

Abstract

Respiratory viruses that emerge in the human population may cause high morbidity and mortality, as well as concern about pandemic spread. Examples are severe acute respiratory syndrome coronavirus (SARS-CoV) and novel variants of influenza A virus, such as H5N1 and pandemic H1N1. Different animal models are used to develop therapeutic and preventive measures against such viruses, but it is not clear which are most suitable. Therefore, this review compares animal models of SARS and influenza, with an emphasis on non-human primates, ferrets and cats. Firstly, the pathology and pathogenesis of SARS and influenza are compared. Both diseases are similar in that they affect mainly the respiratory tract and cause inflammation and necrosis centred on the pulmonary alveoli and bronchioles. Important differences are the presence of multinucleated giant cells and intra-alveolar fibrosis in SARS and more fulminant necrotizing and haemorrhagic pneumonia in H5N1 influenza. Secondly, the pathology and pathogenesis of SARS and influenza in man and experimental animals are compared. Host species, host age, route of inoculation, location of sampling and timing of sampling are important to design an animal model that most closely mimics human disease. The design of appropriate animal models requires an accurate pathological description of human cases, as well as a good understanding of the effect of experimental variables on disease outcome.

Keywords: SARS coronavirus; animal model; influenza; respiratory disease.

Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Lesions in the bronchioles and alveoli of cats, ferrets and cynomolgus macaques infected experimentally with H5N1 influenza virus and SARS-CoV are characterized by DAD and bronchiolitis. HE. Bars, 50 μm (A, E, I and J). Bars, 20 μm (B–D, F–H, K and L).
Fig. 2
Fig. 2
Cell type tropism in the respiratory tract of cats and ferrets infected experimentally with H5N1 influenza virus and SARS-CoV. The presence of receptors is demonstrated for SARS-CoV by the expression of ACE2 by IHC and for H5N1 by the expression of virus attachment by virus histochemistry. The presence of virus in similar cell types is demonstrated by virus antigen expression by IHC. Bars, 10 μm.
Fig. 3
Fig. 3
Virus antigen expression (IHC) and histopathology (HE) of respiratory tissue in ferrets infected with different influenza viruses; seasonal H3N2 (A–D), pH1N1 (E–H) and H5N1 (I–L). Bars, 50 μm (bronchiole). Bars, 25 μm (alveoli).

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